Grimm D, Kromer E P, Böcker W, Bruckschlegel G, Holmer S R, Riegger G A, Schunkert H
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
J Hypertens. 1998 Sep;16(9):1345-55. doi: 10.1097/00004872-199816090-00016.
Left ventricular hypertrophy (LVH) is characterized by remodeling of both myocyte and interstitial compartments of the heart. The aim of this investigation was to study the effects of angiotensin converting enzyme (ACE) inhibition on alterations in the composition of the interstitium in chronic pressure-overload hypertrophy.
LVH was induced in weanling rats by banding the ascending aorta. Animals with aortic banding received either vehicle (n = 20), hydralazine (20 mg/kg per day, n = 20), or the ACE inhibitor ramipril (10 mg/kg per day, n = 20) during weeks 6-12 after banding.
Compared with sham-operated, untreated rats (n = 20), aortic-banded vehicle and hydralazine-treated rats displayed substantially increased left ventricular weights and myocyte diameters whereas ramipril significantly blunted the hypertrophic response at the myocyte level (each P < 0.001) as well as the increase in left ventricular weight (each P < 0.01). In addition, image analysis revealed a significant induction of perivascular and interstitial tissue accumulation in vehicle- and hydralazine-treated rats (2.5-fold, each P < 0.0001). In contrast, ramipril-treated rats displayed attenuated interstitial and perivascular fibrosis, both being significantly diminished compared with vehicle- and hydralazine-treated rats (each P< 0.001). Further, vehicle- and hydralazine-treated rats were characterized by elevated steady-state messenger (m)RNA levels of fibronectin (2.7- and 2.8-fold, P< 0.005), collagen I (2.0- and 1.8-fold, P < 0.0005), collagen III (both 2.2-fold, P < 0.001) and laminin B (1.6- and 1.6-fold, P < 0.005). In parallel, the corresponding immunohistochemical signals were markedly enhanced in these groups. In comparison, ramipril significantly blunted the induction of collagen I and III, laminin B and fibronectin at both the mRNA and protein levels. These morphological and molecular differences between the hydralazine and ramipril groups could not be attributed to differences in left ventricular-pressures, which were markedly elevated in all aortic stenosis rats (1.9-fold, each P < 0.001 versus sham). In fact, given that ramipril but not hydralazine blunted the hypertrophic response to pressure overload, the echocardiographic measurements revealed that left ventricular systolic wall stress was higher in the ramipril group (70 +/- 1 versus 34 +/- 0.7 kdyn/cm2; P < 0.02).
ACE inhibition may limit both myocyte and interstitial remodeling despite ongoing cardiac pressure overload.
左心室肥厚（LVH）的特征是心肌细胞和心脏间质成分的重塑。本研究的目的是探讨血管紧张素转换酶（ACE）抑制对慢性压力超负荷性肥厚中间质成分改变的影响。
通过结扎升主动脉在断奶大鼠中诱导LVH。在结扎后第6 - 12周，接受主动脉结扎的动物分别给予溶剂（n = 20）、肼屈嗪（每天20 mg/kg，n = 20）或ACE抑制剂雷米普利（每天10 mg/kg，n = 20）。
与假手术未治疗的大鼠（n = 20）相比，主动脉结扎的溶剂组和肼屈嗪治疗组大鼠的左心室重量和心肌细胞直径显著增加，而雷米普利在心肌细胞水平显著减弱了肥厚反应（各P < 0.001）以及左心室重量的增加（各P < 0.01）。此外，图像分析显示，溶剂组和肼屈嗪治疗组大鼠的血管周围和间质组织积聚显著增加（均为2.5倍，各P < 0.0001）。相比之下，雷米普利治疗组大鼠的间质和血管周围纤维化减轻，与溶剂组和肼屈嗪治疗组大鼠相比均显著减少（各P < 0.001）。此外，溶剂组和肼屈嗪治疗组大鼠的纤连蛋白、I型胶原、III型胶原和层粘连蛋白B的稳态信使（m）RNA水平升高（分别为2.7倍和2.8倍，P < 0.005；2.0倍和1.8倍，P < 0.0005；均为2.2倍，P < 0.001；1.6倍和1.6倍，P < 0.005）。同时，这些组中相应的免疫组化信号明显增强。相比之下，雷米普利在mRNA和蛋白质水平均显著减弱了I型胶原、III型胶原、层粘连蛋白B和纤连蛋白的诱导。肼屈嗪组和雷米普利组之间的这些形态学和分子差异不能归因于左心室压力的差异，所有主动脉狭窄大鼠的左心室压力均显著升高（与假手术组相比为1.9倍，各P < 0.001）。事实上，鉴于雷米普利而非肼屈嗪减弱了对压力超负荷的肥厚反应，超声心动图测量显示雷米普利组的左心室收缩壁应力更高（70±1对34±0.7 kdyn/cm2；P < 0.02）。
尽管存在持续的心脏压力超负荷，ACE抑制可能会限制心肌细胞和间质重塑。
